Journal Article

Hypothalamic involvement in Huntington's disease: an <i>in vivo</i> PET study

Marios Politis, Nicola Pavese, Yen F. Tai, Sarah J. Tabrizi, Roger A. Barker and Paola Piccini

in Brain

Published on behalf of The Guarantors of Brain

Volume 131, issue 11, pages 2860-2869
Published in print November 2008 | ISSN: 0006-8950
Published online October 2008 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awn244
Hypothalamic involvement in Huntington's disease: an in vivo PET study

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Recent studies have shown alterations in metabolism, sleep and circadian rhythms as well as in several neuropeptides derived from the hypothalamic–pituitary axis in Huntington's disease patients; however, the pathology underlying these abnormalities is not known. Our aim was to assess in vivo D2 receptor's loss/dysfunction and increases in microglial activation in the hypothalamus of symptomatic Huntington's disease patients and premanifest Huntington's disease gene carriers using PET with 11C-raclopride (RAC), a specific D2 receptor ligand and 11C-(R)-PK11195 (PK), a marker of microglial activation. We have studied 9 symptomatic Huntington's disease patients (age = 46.8 ± 4.7 years; mean ± SD) and 10 premanifest Huntington's disease gene carriers (age = 41.9 ± 8.2 years; mean ± SD). RAC and PK findings for these subjects were compared with those of a group of normal controls (RAC, n = 9; PK, n = 10). In the symptomatic Huntington's disease group, we found a significant decrease (P = 0.0012) in mean hypothalamic RAC binding potential (BP) and a significant increase in mean hypothalamic PK BP (P = 0.0008). Similarly, a significant decrease (P = 0.0143) in mean hypothalamic RAC BP and a significant increase in mean hypothalamic PK BP (P = 0.0057) were observed in the premanifest Huntington's disease group. Hypothalamic RAC and PK BP values correlated with each other in combined Huntington's disease groups (r = −0.6180, P = 0.0048) but not with striatal RAC and PK BP values. Our data demonstrate, for the first time, significant D2 receptor loss and microglia activation in the hypothalamus of Huntington's disease. These pathological changes occur very early in the course of the disease and may partly explain the development of commonly reported symptoms in Huntington's disease including progressive weight loss, alterations in sexual behaviour and disturbances in the wake–sleep cycle.

Keywords: hypothalamus; Huntington's disease; positron emission tomography (PET); raclopride; PK11195

Journal Article.  5484 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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